Pharmacokinetics and brain targeting of trans-resveratrol loaded mixed micelles in rats following intravenous administration

Abstract

Trans-Resveratrol (T-RES) is a compound with wide therapeutic applications that shows low bioavailability and distribution across blood-brain barrier. The purpose of our study was to develop T-RES loaded mixed micelle (T-RES-MM) for its enhanced systemic availability and targeting to the brain. T-RES-MMs were formulated using Pluronic F-127 (PF-127) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) by using film hydration process. Formulations were characterized for size of particles, zeta potential, drug efficiency of entrapment, drug loading, and hemolytic study. Further in vivo pharmacokinetic and brain distribution study carried out in Sprague Dawley rats. The nano ranged size for drug-loaded mixed micelles was 21.55 ± 2.15 nm for optimized formulation with PF-127:TPGS (4:1). Formulation with maximum drug loading and entrapment efficiency of 8.4 ± 0.37% and 94.37 ± 1.01% respectively were further used for in vivo study. Percent hemolysis by micelles at all concentrations indicates the biocompatibility and safety for administration by i.v. route. The AUC_0-t for T-RES-MM was 460.98 ± 158.99 h*ng/ml while for T-RES it was 276.27 ± 174.05 h*ng/ml. Drug targeting index suggests successful targeting of T-RES to the brain. Overall findings conclude in prepared T-RES-MM exhibit superiority of formulation as compared to T-RES solution.

Keywords:

• Trans-resveratrol
• film hydration
• mixed micelle
• brain targeting
• pharmacokinetics
• blood–brain barrier

Acknowledgments

Author R. K. is thankful to DBT for fellowship. J. R. G. is thankful to DBT and CSIR for financial support. Authors G. T. and KSP are thankful to the Ministry of Chemicals and Fertilizers for fellowship. M. R. and A. H. are thankful to CSIR and ICMR, respectively, for fellowship. The authors are thankful to the Director, CSIR-CDRI for constant encouragement and support. CDRI communication number: 9990.

Disclosure statement

The authors declare that there is no potential conflict of interest.